Reacción #2275716

Ecuación de reacción

3-hydroxypicolinic acid

diisopropylethylamine

1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide

EDCI

1-hydroxybenzotriazole

glycine tert-butyl ester HCl

→

desired compound

Rendimiento 22.0%

[(3-hydroxy-pyridine-2-carbonyl)-amino]-acetic acid tert-butyl ester

Rendimiento 22.0%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONis introduced
2. 2
   Concentraciónthen concentrated under reduced pressure
3. 3
   workup.ADDITIONThe reaction mixture is diluted with EtOAc
4. 4
   Lavadothen washed with 1M HCl, sat. NaCl
5. 5
   Secadothe organic layer is dried (MgSO4)
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated under reduced pressure to a crude oil that
8. 8
   Otrois purified over silica (EtOAc/heptane 1:4)

Procedimiento

To a solution of 3-hydroxypicolinic acid (0.20 g, 1.44 mmol) in DMF (5 mL) at 0° C. under N2 is added diisopropylethylamine (DIPEA) (0.75 ml, 4.3 mmol), 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide (EDCI) (0.412 g, 2.9 mmol) and 1-hydroxybenzotriazole (HOBt) (0.019 g, 0.14 mmol). The resulting mixture is stirred for 5 min before glycine tert-butyl ester HCl (0.36 g, 2.9 mmol) is introduced. The resulting solution is stirred at room temperature for 3 days then concentrated under reduced pressure. The reaction mixture is diluted with EtOAc then washed with 1M HCl, sat. NaCl, and the organic layer is dried (MgSO4), filtered and concentrated under reduced pressure to a crude oil that is purified over silica (EtOAc/heptane 1:4) to afford 0.078 g (22% yield) of the desired compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 11.80 (1H, s), 8.39 (1H, br s), 8.02 (1H, dd, J=4.4, 1.5 Hz), 7.27 (1H, dd, J=8.8, 4.4 Hz), 7.25 (1H, dd, J=8.4, 1.5 Hz), 4.06 (2H, d, J=5.5 Hz), 1.44 (9H, s). HPLC-MS: m/z 197 [M-tBu]+.

Fuente